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Regulation of a metabolic pathway
- tryptophan can both
- (a) inhibit the activity of the first enzyme in the pathway (feedback inhibition)
- (b) Regulation of gene expression/ enzyme production
- The switch is a segment of DNA
- controls the access of RNA polymerase to the genes
operon ( Prokaryotic/ Bacteria)
entire stretch of DNA required for enzyme production for the tryptophan pathway
trp operon in E. coli (repressive)
- Genes: TrpE -> TrpA
- Tryptophan present, repressor active, operator off/ operon off
turn on operator, preventing transcription of the genes
- asmall molecule that cooperates with a repressor protein to switch an operon off
- Ex. Tryptophan
lac operon (Inducible)
- lacZ, lacY, lacA
- lac repressor,in contrast, is active by itself
- inducer(allolactose), inactivates the repressor
- Lactose present, repressor inactive, operon on.
- Lactorse-> remove repressor -> operon ON!
- neg control by repressor, positive by CAP
cyclic AMP (cAMP)
- when glucose is scarce-> cAMP is high -> active ap -> increases the affinity of RNA polymerase
- activator (cap) a protein that binds to DNA and stimulates transcriptionof a gene.
- when glucose present/ cAMP is low -> little lac mRNA synthesized
differential gene expression (Eu.)
the expression of different genes by cells with the same genome
Regulation of Chromatin Structure
- The location of agene’s promoter ror nuclear laminacan affect whether the gene is transcribed
- chemical modifications tothe histone proteins and to the DNA of chromatin can influence both chromatin structure and gene expression.
effect of histone acetylation
- Histone tails protrude outward from a nucleosome/ accessible for chemical modification
- Acetylation of histone tails promotes loose chromatin structure that permits transcription
- addition of methyl groups to certain bases
- inactivation of genes/alleles
Inheritance of traits transmitted by mechanisms not directly involving the nucleotidesequence
segments of noncoding DNA that serve as binding sites for the proteins called transcription factors,which in turn regulate transcription
- distal control elements
- rate of gene expression can be increased or decreased by binding specifice transcription factors, activators/ repressors
- Bending of the DNA by a protein enables enhancers to influence a promoter
Protein-mediated bending of
bring the bound activators into contact with a group of mediator proteins, which in turn interact with proteins at the promoter.
Chromosomal interactions in the interphase nucleus.
Although each chromosome has its own territory loops of chromatin may extend into othersites in the nucleus.
alternative RNA splicing, different mRNA molecules are produced from the same primary transcript, dependingo n which RNA segments are treated as exons and which as introns.
- cell commonly attaches moleculesof a small protein(ubiquitin) to proten for destruction
- recognize by proteasome -> fragments(petides)
- Alternative mRNA splicing
- Translation initiation
- Protein degradation
- Only a small fraction of DNA codes for proteins
- RNA interference: The process of inhibiting gene expression using RNA molecules
- - MicroRNAs: small single-stranded RNA molecules that can bind to mRNA
- cancer-causing genes
- found in the genomes of humans and other animals
code for proteins that stimulate normal cell growth and division
proto-oncogenes to oncogenes
- movement of DNA within the genome
- amplification of a proto-oncogene
- point mutations in a control element or in the proto-oncogene itself (promoter or enhancer, the coding sequence
- proteins they encode help prevent uncontrolled cell growth.
- repair damaged DNA,
- control the adhesion of cells to each other or to the extracellula rmatrix
- G protein that relays a signal from a growth factor receptor on the plasma membrane to a cascade of protein kinases
- lead to production of a hyperactive Ras protein that triggers the kinase cascade -> increased cell division/ excessive cell growth
- tumor suppressor gene
- prevents a cell from assing on mutations due to DNA damage – it halts the cell cycle
- Multiple mutations are generally needed for
- full-fledged cancer; thus the incidence increases with age
- individuals can inherit oncogenes or mutant alleles of tumor-suppressor genes
- Example: Breast Cancer - BRCA1 & BRAC2 genes